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Biomedical subjects

S Kindler

Publications and source records attributed to S Kindler.

At least 37 records · Page 2Linked to original sources
PubMed1996

SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo.

Synapse-associated proteins (SAPs) are constituents of the pre- and postsynaptic submembraneous cytomatrix. Here, we present SAP102, a novel 102kDa SAP detected in dendritic shafts and spines of asymmetric type 1 synapses. SAP102 is enriched in preparations of synaptic junctions, where it biochemically behaves as a component of the cortical cytoskeleton. Antibodies directed against NMDA receptors coimmunoprecipitate SAP102 from rat brain synaptosomes. Recombinant proteins containing the carboxy-terminal tail of NMDA receptor subunit NR2B interact with SAP102 from rat brain homogenates. All three PDZ domains in SAP102 bind the cytoplasmic tail of NR2B in vitro. These data represent direct evidence that in vivo SAP102 is involved in linking NMDA receptors to the submembraneous cytomatrix associated with postsynaptic densities at excitatory synapses.

Amino Acid Sequence↗
PubMed1996

Synaptic proteins and the assembly of synaptic junctions.

Synapses are highly specialized contact sites between neurons and their target cells where information in the form of chemical substances travels from a pre- to a postsynaptic cell. In the central nervous system of mammals, most nerve cells are innervated by functionally distinct types of synapses, each requiring a specific set of molecular constituents for proper function. Various molecular players that may be involved in the assembly of synaptic junctions have been identified recently.

Journal Article↗
PubMed1996

MAP2a, an alternatively spliced variant of microtubule-associated protein 2.

MAP2, a dendritically localized microtubule-associated protein (MAP), consists of a pair of high molecular mass (280 kDa) polypeptides, MAP2a and MAP2b, and several low molecular mass (70 kDa) proteins called MAP2c. Although MAP2b and MAP2c have been shown to arise via alternative splicing. It was not clear whether MAP2a is also created by alternative splicing or by posttranslational modification. Using epitope peptide mapping, we have demonstrated that an element specific to MAP2a is situated at its N-terminal end. A cDNA clone from an adult rat brain library was found to contain an additional 246 nucleotides situated at the 5' end of the 9-kb MAP2 mRNA. Antibodies generated against the encoded protein sequence recognize specifically MAP2a in rat brain homogenates. Moreover, although MAP2a, like MAP2b, is found in dendrites and cell bodies, its temporal appearance and cell type-specific distribution in rat brain differs from MAP2b.

Aging↗
PubMed1996

Piccolo, a novel 420 kDa protein associated with the presynaptic cytomatrix.

In this study, we describe a novel 420 kDa protein, called Piccolo, found at a wide variety of adult rat brain synapses. High protein levels in the cerebellum, the olfactory bulb and the hippocampus were frequently observed to be associated with asymmetric type 1 synapses. Piccolo is selectively enriched in presynaptic terminals, but is not a component of synaptic vesicles (SVs). Immunogold electron microscopy revealed that Piccolo localizes to the amorphous material among SVs at the presynaptic plasma membrane. Biochemical studies showed that it is very tightly bound to this structure. Thus, we speculate that Piccolo is a structural component of the presynaptic cytomatrix which anchors SVs to the presynaptic plasmalemma.

Animals↗
PubMed1995

Antidepressant and cognitive effects of twice- versus three-times-weekly ECT.

OBJECTIVE: The purpose of this study was to determine which of the two commonly used schedules of ECT administration, twice or three times weekly, is clinically optimal in terms of antidepressant efficacy and cognitive effects. METHOD: In this double-blind study, 52 consenting, medication-free patients with major depressive disorder, endogenous subtype (Research Diagnostic Criteria), were randomly assigned to bilateral, brief-pulse, constant-current ECT administered over 4 weeks at a rate of three times weekly or twice weekly with the addition of one simulated ECT (anesthesia and muscle relaxant only) per week. Outcome measures were the Hamilton Depression Rating Scale, Acute Cognitive Effects Battery, and Chronic Cognitive Effects Battery. RESULTS: Hamilton depression scale scores were significantly improved by both schedules, with no difference in outcome either 1 week or 1 month after the end of the ECT series. However, the rate of response to ECT three times a week was significantly faster and was related to the rate of real ECT administration. Cognitive effects were more prominent with ECT three times a week. CONCLUSIONS: ECT twice a week is an effective schedule for clinical practice and is potentially advantageous in view of a therapeutic outcome identical to that of ECT three times a week and less severe cognitive effects. ECT three times a week may be specifically indicated when early onset of clinical effect is of primary importance.

Adult↗
PubMed1994

Olfactory sensitivity in major depressive disorder and obsessive compulsive disorder.

Olfactory sensitivity to two odorants, isoamyl acetate and androsterone, was assessed in 14 obsessive compulsive disorder (OCD) patients, nine major depressive disorder (MDD) patients, and 16 sex- and age-matched healthy controls. Tests were performed during a drug-free period, and 3 and 6 weeks after initiation of antidepressant drug therapy. No difference in olfactory sensitivity, to either odorant, was found between OCD patients and controls at any time. In MDD patients, a significant increase in the sensitivity to isoamyl acetate was observed 6 weeks after initiation of treatment, compared to controls.

Adult↗
PubMed1994

Long-chain fatty acids decrease lipoprotein lipase activity of cultured rat adipocyte precursors.

The effect of fatty acids on rat adipocyte precursor lipoprotein lipase (LPL) activity was examined. Cellular LPL activity in cultured perirenal precursors reached a maximum after 6 days. At day 6, addition of 10(-8) mol/L oleic acid to the culture medium for 6 hours resulted in a significant reduction of LPL activity. Exposing cultured precursors to 10(-4) mol/L oleic acid caused more than a 50% decrease of intracellular LPL activity measured in either acetone-ether or detergent extracts and more than a 60% decrease of heparin-releasable LPL activity. These reductions were evident within 2.5 hours of exposure to oleic acid, and exposure to oleic acid for as little as 15 minutes caused a subsequent decrease in LPL activity. LPL activity recovered 48 hours after removal of oleic acid from culture medium. Decreased LPL activity after oleic acid exposure was also noted in epididymal cells and in differentiated adipocyte precursors. The extent of decrease of LPL activity upon fatty acid exposure was dependent on the presence of the carboxyl group and was affected by acyl chain length. Although oleic acid did not affect protein synthesis estimated by [3H]-leucine incorporation, LPL mRNA levels were decreased following exposure of cells to oleic acid. Glycerol-3-phosphate dehydrogenase (G3PD) activity and mRNA levels were not affected by oleic acid exposure. Hence, fatty acids cause a dose-, acyl chain-, and carboxyl group-dependent specific decrease of heparin-releasable and intracellular LPL activities in cultured rat adipocyte precursors; this effect is associated with and is likely caused at least in part by a decrease in LPL mRNA levels.

Adipocytes↗
PubMed1994

Four repeat MAP2 isoforms in human and rat brain.

In mammalian brain, variations in the primary structure of the characterized microtubule-associated protein 2 (MAP2) isoforms have only been observed in their projection domains whose length determines the spacing between neighboring microtubules. We now report that, as with MAP4 and tau, MAP2 isoforms containing four (4R) instead of three (3R) tandem repeats in their microtubule binding domains do exist in human and rat brain. The additional sequence, inserted between the first and second repeat of the 3R-MAP2 messages, appears on mRNAs encoding both high and low molecular weight (Hwt and Lwt) rat MAP2 variants. In contrast to the corresponding 3R-messages, 4R-Hwt MAP2 concentrations decrease during early postnatal rat brain development, while the amount of 4R-Lwt MAP2 messages remains constant. In general, 4R-/3R-MAP2 mRNA ratios appear to be low with the highest levels of 4R-messages found in the cerebellum.

Alternative Splicing↗
PubMed1994

Effects of age and anatomic site on preadipocyte number in rat fat depots.

Preadipocytes are cells which are capable of either replication or of differentiation into fat cells. As with other stem or progenitor cell types, the replicative capacity of preadipocytes declines with increasing age; however, little information about effects of age on preadipocyte cell number in vivo is available. We determined preadipocyte number in the perirenal and epididymal fat depots of 3-, 17-, and 27-month-old Fischer 344 rats in 23 experiments. Increasing age was not associated with a decrease in preadipocyte number; indeed, the number of preadipocytes increased in epididymal depots throughout maturation and senescence. Hence, the tenet that aging causes a decline in the size of stem cell or progenitor pools is not generalizable to all tissues, even if the cells exhibit reduced replicative capacity in culture.

Adipocytes↗
PubMed1992

Hormone responses to fenfluramine and placebo challenge in endogenous depression.

Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.

Adult↗
PubMed1992

Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression.

Prolactin release in response to fenfluramine hydrochloride (60 mg orally) and placebo was evaluated in 18 medication-free patients with RDC major depressive disorder, endogenous subtype, before and after a series of bilateral treatments with ECT. Before ECT, fenfluramine induced a twofold increase in plasma prolactin levels. This response was significantly enhanced after the ECT series, while baseline prolactin levels and response to the placebo challenge were not altered. There was no significant difference in plasma fenfluramine and norfenfluramine levels during the pre- and post-ECT challenges. These findings suggest that ECT enhances central serotonergic responsivity and extend to depressed patients pre-clinical observations regarding the effect of electroconvulsive shock on serotonergic function.

Depressive Disorder↗
PubMed1992

Effect of hypophysectomy on rat preadipocyte replication and differentiation.

The effects of hypophysectomy, which results in decreased fat pad weight, fat cell number, and new fat cell formation, on preadipocyte replication were examined. Perirenal and epididymal preadipocytes were cultured from hypophysectomized, sham-operated and unoperated 3-month-old rats. In cloned preadipocytes, hypophysectomy resulted in a 19% decrease in cloning efficiency and a 60% reduction in cell number after 3 weeks in culture. Perirenal cells underwent more extensive replication than epididymal cells. The mechanism of reduced replication following hypophysectomy differed from that of donor site: hypophysectomy resulted in an increased percentage of cells which underwent 2 or fewer population doublings at the expense of cells capable of more than 2 doublings. However, donor site had little effect specifically on these slowly replicating preadipocytes; rather, perirenal preadipocytes underwent more extensive replication than epididymal cells because of the higher percentage of preadipocytes capable of 13 or more doublings in perirenal fat pads. Hypophysectomy did not result in decreased differentiation of preadipocytes. These observations are in accord with the hypothesis that hypophysectomy reduces fat cell number in maturing rats partly through an effect on preadipocyte replicative capacity. Additionally, it seems that more than one form of preadipocyte exists, the various forms having differing susceptibilities to factors such as pituitary function and anatomic site.

Adipose Tissue↗
PubMed1992

Current concepts in the pharmacological treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD is characterised by intrusive, unwanted and persistently recurring mental events (obsessions) that usually evoke discomfort or anxiety, and/or repetitive ritualistic behaviours (compulsions) that are aimed at reducing discomfort and anxiety. However, the compulsions succeed only in achieving transient relief, followed by a growing sense of pressure. 10 years ago, OCD was considered a rare and treatment-refractory disorder. Recent well designed studies document a lifetime prevalence rate for OCD of more than 2% in the general population. The outlook for patients with OCD has changed in the last decade, with many well controlled studies showing that OCD patients respond to specific behavioural and pharmacological treatments. The specific form of behavioural therapy is in vivo exposure coupled with response prevention. Only serotonin reuptake inhibitors, such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack the anticholinergic side effects of clomipramine and, thus, provide an alternative treatment for patients who cannot tolerate clomipramine. Other nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and anxiolytic agents have not been found to be consistently effective in this disorder. Insufficient data on the efficacy of neuroleptics and their potentially irreversible side effects limit their use in OCD patients. Behavioural and the pharmacological treatment are complementary, and a combination of the 2 therapies is apparently more effective than either modality alone.

Clomipramine↗